The Centers for Disease Control recommendation for amantadine to control nursing home influenza A outbreaks is "rapid administration to staff and all residents when outbreaks occur for the duration of influenza activity in the community". This recommendation is disconcerting because: 1) of limited data of its efficacy in nursing home outbreaks; 2) absence of controlled prospective studies demonstrating the ability of amantadine to reduce influenza or its complications in the nursing home setting; 3) of the toxicity associated with amantadine use in the elderly; 4) of the potential transmission of resistant viruses in the presence of amantadine; and 5) the ambiguity of 'community' and therefore the recommended duration of prophylaxis. Our laboratory focus has been on the effect of age upon vaccine response, influenza susceptibility, and drug toxicity in elderly people and has led to our current interest in amantadine prophylaxis and treatment. We recently demonstrated the emergence and transmission of amantadine resistant iffluenza A viruses and more severe amantadine associated toxicity than previously believed in the nursing home setting. Assuming that amantadine prophylaxis (in distinction to amantadine treatment) in the nursing home can effectively limit influenza outbreaks, we hypothesize that: 1) fewer cases of influenza A will arise on nursing home floors where clinical cases of influenza treated with amantadine are removed from the home for the duration of their treanmnt; 2) amantadine, when used to limit influenza outbreaks in the nursing home setting, will have reduced toxicity with a shorter duration of prophylaxis; 3) emergence of amantadine resistant influenza strains will occur independent of the serum amantadine level; and, 4) duration of amantadine prophylaxis should be based on presence of influenza A within the nursing home, and not the community at large. The proposed 5 year study will involve the majority of subjects residing at a 685 bed rural nursing home. We will document vaccine response by measuring influenza antibody titers, monitor subjects to identify respiratory illnesses and influenza infections, and once influenza is diagnosed, intervene with a prescribed treatment program that will involve irspiratory isolation and amantadine administration. We will also determine clinical amantadine toxicity, amantadine levels, and characterize amantadine resistant influenza as compare with amantadine levels and the associated illness. At the conclusion of this prospective clinical trial, we will have a sound basis for future recommendations regarding the use of amantadine in nursing homes during the influenza season for both rural and urban settings that will include strategies to minimize toxicity.